Targeting the endoplasmic reticulum with a membrane-interactive luminescent ruthenium(ii) polypyridyl complex† †Electronic supplementary information (ESI) available: Experimental details, characterization of 2 and Fig. S1–S6. See DOI: 10.1039/c3sc51725j Click here for additional data file

• Published in: Chemical science (Cambridge) 2013-10, Vol.4 (12), p.4512-4519
• Main Authors: Gill, Martin R., Cecchin, Denis, Walker, Michael G., Mulla, Raminder S., Battaglia, Giuseppe, Smythe, Carl, Thomas, Jim A.
• Format: Article
• Language: English
• Subjects: Chemistry
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c3sc51725j

The characterization and bioactivity of the dinuclear ruthenium( ii ) complex [(Ru(DIP) 2 ) 2 (tpphz)] 4+ (DIP = 4,7-diphenyl-1,10-phenanthroline and tpphz = tetrapyrido[3,2- a :2′,3′- c :3′′,2′′- h :2′′′,3′′′- j ]phenazine) is reported. The characterization and bioactivity of the dinuclear ruthenium( ii ) complex [(Ru(DIP) 2 ) 2 (tpphz)] 4+ (DIP = 4,7-diphenyl-1,10-phenanthroline and tpphz = tetrapyrido[3,2- a :2′,3′- c :3′′,2′′- h :2′′′,3′′′- j ]phenazine) is reported. This new complex is found to be luminescent in acetonitrile, where excitation into MLCT (metal-to-ligand charge-transfer) bands in the visible area of the spectrum ( λ ex = 450 nm, ε = 45 000 M –1 cm –1 ) result in red emission ( λ em,max = 620 nm, Φ MLCT = 0.017). Aqueous in vitro binding studies indicate that this complex binds to duplex DNA with an affinity of 1.8 × 10 6 M –1 through a non-classical groove-binding interaction, however, unlike the parent complex [(Ru(phen) 2 ) 2 (tpphz)] 4+ (phen = 1,10-phenanthroline), it also displays an increase in MLCT luminescence on addition of liposomes. Confocal microscopy and TEM studies show that this lipophilic complex targets the endoplasmic reticulum of eukaryotic cells, where it functions as an imaging agent for this organelle, and cytotoxicity studies in human cancer cell lines indicate a comparable potency to the anti-cancer drug cisplatin.